N-Hydroxylation of N-arylacetamides is believed to form intermediates that cause the toxicities of these compounds. We have previously shown that sulfation or glucuronidation of N-hydroxyphenacetin leads to the formation of a reactive metabolite whereas with N-hydroxy-2-acetylaminofluorene only sulfation leads to a reactive metabolite. The half-lives of the N-hydroxyphenacetin conjugates, however are different. The sulfate conjugate immediately rearranges to a reactive metabolite whereas phenacetin N-O-glucuronide slowly rearranges (half-live 8.7. hour). The glucuronide of N-hydroxyphenacetin has been isolated and the pattern of the decomposition products formed in buffers were studied. Three primary products were formed: phenacetin, 2-hydroxyphenacetin glucuronide, and N-acetylimidoquinone. Since N-acetylimidoquinone is chemically reactive, it covalently binds to protein, reacts with glutathion to form an acetaminophen conjugate, is reduced by ascorbin acid or other reducing agents to acetaminophen and is hydrolyzed to acetamide and quinone. The same reactive metabolite was found by sulfation of N-hydroxyphenacetin.